11-63304838-C-T

Variant names:

• chr11-63304838-C-T
• rs1201559
• NM_001039752.4:c.1547C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039752.4(SLC22A10):​c.1547C>T​(p.Pro516Leu) variant causes a missense change. The variant allele was found at a frequency of 0.548 in 1,613,444 control chromosomes in the GnomAD database, including 247,086 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (18863 hom., cov: 32)
  • Exomes 𝑓: 0.55 (228223 hom.)
• Consequence: SLC22A10 NM_001039752.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82
• Publications: 39 publications found

Genes affected

SLC22A10 (HGNC:18057): (solute carrier family 22 member 10) Predicted to enable transmembrane transporter activity. Predicted to be involved in organic anion transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.385808E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039752.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A10	NM_001039752.4	MANE Select	c.1547C>T	p.Pro516Leu	missense	Exon 9 of 10	NP_001034841.3
	SLC22A10	NR_134874.2		n.1415C>T		non_coding_transcript_exon	Exon 10 of 11

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A10	ENST00000332793.11	TSL:1 MANE Select	c.1547C>T	p.Pro516Leu	missense	Exon 9 of 10	ENSP00000327569.6
	SLC22A10	ENST00000533483.5	TSL:1	n.*133C>T		non_coding_transcript_exon	Exon 10 of 11	ENSP00000433048.1
	SLC22A10	ENST00000533483.5	TSL:1	n.*133C>T		3_prime_UTR	Exon 10 of 11	ENSP00000433048.1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73404 AN: 151904 Hom.: 18871 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.500

GnomAD2 exomes AF: 0.520 AC: 129602 AN: 249020 AF XY: 0.523

Gnomad AFR exome AF: 0.297

Gnomad AMR exome AF: 0.509

Gnomad ASJ exome AF: 0.444

Gnomad EAS exome AF: 0.421

Gnomad FIN exome AF: 0.606

Gnomad NFE exome AF: 0.578

Gnomad OTH exome AF: 0.536

GnomAD4 exome AF: 0.555 AC: 810684 AN: 1461422 Hom.: 228223 Cov.: 59 AF XY: 0.553 AC XY: 401901 AN XY: 727024

African (AFR) AF: 0.283 AC: 9455 AN: 33448

American (AMR) AF: 0.505 AC: 22578 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 11229 AN: 26128

East Asian (EAS) AF: 0.413 AC: 16383 AN: 39676

South Asian (SAS) AF: 0.459 AC: 39571 AN: 86254

European-Finnish (FIN) AF: 0.609 AC: 32525 AN: 53410

Middle Eastern (MID) AF: 0.490 AC: 2823 AN: 5766

European-Non Finnish (NFE) AF: 0.579 AC: 643767 AN: 1111694

Other (OTH) AF: 0.536 AC: 32353 AN: 60372

GnomAD4 genome AF: 0.483 AC: 73411 AN: 152022 Hom.: 18863 Cov.: 32 AF XY: 0.482 AC XY: 35848 AN XY: 74322

African (AFR) AF: 0.301 AC: 12471 AN: 41498

American (AMR) AF: 0.505 AC: 7706 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1513 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2247 AN: 5164

South Asian (SAS) AF: 0.456 AC: 2195 AN: 4818

European-Finnish (FIN) AF: 0.598 AC: 6312 AN: 10550

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.578 AC: 39307 AN: 67948

Other (OTH) AF: 0.499 AC: 1052 AN: 2108

Alfa AF: 0.543 Hom.: 75080

Bravo AF: 0.471

TwinsUK AF: 0.574 AC: 2130

ALSPAC AF: 0.571 AC: 2201

ESP6500AA AF: 0.294 AC: 1127

ESP6500EA AF: 0.568 AC: 4689

ExAC AF: 0.519 AC: 62659

Asia WGS AF: 0.474 AC: 1649 AN: 3478

EpiCase AF: 0.569

EpiControl AF: 0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.47
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.00014	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.8	H
PhyloP100		3.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.27
MPC		0.12
ClinPred		0.072	T
GERP RS		2.7
Varity_R		0.94
gMVP		0.80
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1201559; hg19: chr11-63072310; COSMIC: COSV60420735; COSMIC: COSV60420735;